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Gates Open Research Gates Open Research 2019, 3:1632 Last Updated: 27 JUL 2021 Gates Open Research Gates Open Research 2019, 3:1632 Last updated: 27 JUL 2021 OPEN LETTER Insights from quantitative analysis and mathematical modelling on the proposed WHO 2030 goals for soil- transmitted helminths [version 2; peer review: 2 approved] NTD Modelling Consortium discussion group on soil-transmitted helminths v2 First published: 23 Oct 2019, 3:1632 Open Peer Review https://doi.org/10.12688/gatesopenres.13077.1 Latest published: 04 Dec 2019, 3:1632 https://doi.org/10.12688/gatesopenres.13077.2 Reviewer Status Invited Reviewers Abstract Soil-transmitted helminths (STHs) are a group of parasitic worms that 1 2 infect humans, causing a wide spectrum of disease, notably anaemia, growth retardation, and delayed cognitive development. The three version 2 main STHs are Ascaris lumbricoides, Trichuris trichiura and hookworm ( (revision) Necator americanus and Ancylostoma duodenale). Approximately 1.5 04 Dec 2019 billion people are infected with STHs worldwide. The World Health Organization goal for 2030 is morbidity control, defined as reaching version 1 <2% prevalence of medium-to-high intensity infections in preschool- 23 Oct 2019 report report age children and school-age children (SAC). Treatment guidelines for achieving this goal have been recommended. The Neglected Tropical 1. Rubina Imtiaz , The Task Force for Global Diseases Modelling Consortium has developed mathematical and statistical models to quantify, predict, and evaluate the impact of Health, Decatur, USA control measures on STHs. These models show that the morbidity target can be achieved following current guidelines in moderate 2. Suzy J. Campbell , Evidence Action: prevalence settings (20-50% in SAC). In high prevalence settings, semi- Deworm the World Initiative, Washington, annual preventive chemotherapy (PC) ideally including adults, or at USA least women of reproductive age, is required. For T. trichiura, dual therapy with albendazole and ivermectin is required. In general, Any reports and responses or comments on the stopping PC is not possible without infection resurgence, unless article can be found at the end of the article. effective measures for improved access to water, hygiene, and sanitation have been implemented, or elimination of transmission has been achieved. Current diagnostic methods are based on egg counts in stool samples, but these are known to have poor sensitivity at low prevalence levels. A target threshold for novel, more sensitive diagnostics should be defined relative to currently preferred diagnostics (Kato-Katz). Our analyses identify the extent of systematic non-access to treatment and the individual patterns of compliance over multiple rounds of treatment as the biggest unknowns and the main impediment to reaching the target. Moreover, the link between morbidity and infection intensity has not been fully elucidated. By providing more insights on all the above, we aim to inform discussions on the goals and treatment guidelines for STHs. Page 1 of 13 Gates Open Research Gates Open Research 2019, 3:1632 Last updated: 27 JUL 2021 Keywords Soil-transmitted helminths, WHO guidelines, morbidity control, NTD Modelling This article is included in the 2030 goals for neglected tropical diseases collection. Corresponding author: NTD Modelling Consortium discussion group on soil-transmitted helminths ([email protected]) Competing interests: No competing interests were disclosed. Grant information: This work was supported by the Bill and Melinda Gates Foundation [OPP1184344]. Luc E. Coffeng was supported by a personal grant from the Dutch Research Council (Nederlandse Organisatie voor Wetenschappelijk Onderzoek [016.Veni.178.023]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2019 NTD Modelling Consortium discussion group on soil-transmitted helminths. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: NTD Modelling Consortium discussion group on soil-transmitted helminths. Insights from quantitative analysis and mathematical modelling on the proposed WHO 2030 goals for soil-transmitted helminths [version 2; peer review: 2 approved] Gates Open Research 2019, 3:1632 https://doi.org/10.12688/gatesopenres.13077.2 First published: 23 Oct 2019, 3:1632 https://doi.org/10.12688/gatesopenres.13077.1 Page 2 of 13 Gates Open Research 2019, 3:1632 Last updated: 27 JUL 2021 The three main STHs are roundworm (Ascaris lumbricoides), REVISED Amendments from Version 1 whipworm (Trichuris trichiura) and hookworm (Necator Minor edits were made to clarify the following issues highlighted americanus and Ancylostoma duodenale). STHs reduce the by Reviewer 2: nutritional status of infected individuals1. In particular, infected 1) Achieving 75% community-wide treatment is especially children can be affected by reduced physical fitness and important to reach the morbidity target for hookworm. impaired growth and cognitive development1. Hookworm 2) Elimination of transmission can be reached in low-transmission infection in women of reproductive age (WRA) can lead to settings. The study on which this insight is based used the basic severe anaemia1. Infections with A. lumbricoides and hookworms reproductive number as a measure of transmission intensity, not prevalence. can be treated effectively with benzimidazole drugs (albenda- 3) All simulation studies have been run for the different STH zole, mebendazole). However, benzimidazoles are less effec- species (Ascaris lumbricoides, Trichuris trichiura, and hookworm tive against T. trichiura. Dual treatment with albendazole and species). Insights are, therefore, species-specific. ivermectin increases treatment efficacy for T. trichiura2–4. 4) The results and conclusion with regard to the importance of Currently, albendazole and mebendazole are donated to the WASH are based on simulations for the impact of sanitation and World Health Organization (WHO) for distribution to affected hygiene measures in isolation and in combination. populations. Any further responses from the reviewers can be found at the end of the article The WHO has announced morbidity control as the main public health target for STHs to be achieved by 2030. According to the most recent WHO guidelines, morbidity control is Disclaimer defined as <2% prevalence of medium-to-high intensity (M&HI) The views and opinions expressed in this article are those of the infections in preschool-age children (preSAC) and school-age authors and do not necessarily reflect the views of the World children (SAC). WHO treatment guidelines advise preventive Health Organization. Publication in Gates Open Research does chemotherapy (PC) by mass drug administration (MDA) to not imply endorsement by the Gates Foundation. achieve morbidity control. Previously, WHO recommended school-based PC without including adults. The most recent Background guidelines recommend PC targeted at preSAC, SAC and Soil-transmitted helminth (STH) infections are caused by WRA. The frequency of PC is based on the prevalence of several species of parasitic worms that are transmitted by eggs STH infections in SAC prior to the start of treatment (see present in human faeces, which contaminate the soil in areas decision tree in Figure 1 for WHO guidelines up until 2019). with poor sanitation. STHs cause some of the most common The recommended PC coverage is 75% in all targeted infections, with about 1.5 billion people infected worldwide1. populations. Figure 1. World Health Organization (WHO) decision tree showing the current WHO guidelines to achieve morbidity control in school-aged children (SAC) using 75% coverage in SAC (black and orange boxes). The bright red boxes represent the modified guidelines assuming 75% community-wide coverage (pre-SAC, SAC, and adults to replace the middle row of boxes that represent the current guidelines. This figure has been adapted from Figure 1 in 5 under a CC-BY 4.0 license. Page 3 of 13 Gates Open Research 2019, 3:1632 Last updated: 27 JUL 2021 Mathematical models of STH transmission dynamics and achieve the 2020 morbidity target in settings where the the impact of interventions have been developed to evaluate prevalence was moderate (20% to 50% in SAC) prior to the start optimal treatment strategies for achieving the WHO goals. The of PC5. For higher prevalence settings, community-wide PC Neglected Tropical Diseases Modelling Consortium (NTDmc) and/or targeting of WRA will be necessary to achieve the funded by the Bill and Melinda Gates Foundation brings morbidity target, especially for hookworm5,8, and/or dual together research groups from multiple scientific institutions therapy with albendazole and ivermectin for T. trichiura5,9. working on neglected tropical diseases (NTDs), including STHs. Implementing PC twice-yearly also increases chance to achieve Modelling groups based at Erasmus Medical Center (EMC) the morbidity target for STH5. Scaling down or stopping PC in Rotterdam and Imperial College London (ICL) have led the as per WHO treatment guidelines is very likely to lead to resur- recent work on STHs. A model comparison was carried out gence of infection to levels above the morbidity target, unless for the EMC and ICL STH models6. Moreover, joint papers transmission conditions are addressed with water, sanitation evaluating WHO treatment guidelines
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